Metal salts of bis-thioureido-benzenes

ABSTRACT

THE COMPOUNDS HAVING EITHER FORMULA   1-(R-Y-CO-NH-C(=S)-N(-R2)-),2-(R1-Y-CO-NH-C(=S)-N(-R3)-),   (X)N-BENZENE, OR THE METAL SALT OF THE COMPOUND WHERE   METAL (M) IS COMPLEXED WITH BOTH CARBONYL AND THIO GROUPS   WHEREIN EACH OF R AND R1 REPRESENTS ALKYL OF 1 TO 12 CARBON ATOMS, ALKYL OF 1 TO 2 CARBON ATOMS SUBSTITUTED WITH HALOGEN, METHOXY OR PHENYL, ALKENYL HAVING 2 TO 3 CARBON ATOM S, ALKYNYL HAVING 2 TO 3 CARBON ATOMS, ARYL OR ARYL SUBSTITUTED WITH HALOGEN, NITRO OR METHYL; EACH OF R2 AND R3 REPRESNETS HYDROGEN OR METHYL; X REPRESENTS HALOGEN, NITRO OR METHYL; N REPRESENTS INTEGER OF 0-3; Y REPRESENTS OXYGEN OR SULFUR AND M REPRESENTS METAL) ARE PREPARED IN ACCORDANCE WITH THE FOLLOWING EQUATIONS:   1-(R2-NH-),2-(R3-NH-),(X)N-BENZENE AND (S=C=N-CO-Y-R)2 -&gt;   1-(R-Y-CO-NH-C(=S)-N(-R2)-),2-(R1-Y-CO-NH-C(=S)-N(-R3)-),   (X)N-BENZENE AND (M&#39;&#39;-OH)2 -&gt; 1-(R-Y-CO-N(-M&#39;&#39;)-C(=S)-   N(-R2)-),2-(R1-Y-CO-N(-M&#39;&#39;)-C(=S)-N(-R3)-),(X)N-BENZENE   AND M(++) -&gt; (R-Y-C(-O(-))=N-C(-S(-))-N(-R2)-((X)N-1,2-   PHENYLENE)-N(-R3)-C(-S(-))=N-C(-O(-))-Y-R1) M(+4)   WHEREIN M&#39;&#39; REPRESENTS ALKALI METAL ATOM AND THE NOVEL COMPOUNDS HAVE BROAD FUNGICIDAL ACTIVITY WITH VERY LOW MAMMALIAN TOXICITY.

United States Patent US. Cl. 260-4381 7 Claims ABSTRACT OF THE DISCLOSURE The compounds having either formula (wherein each of R and R represents alkyl of l to 12 carbon atoms, alkyl of 1 to 2 carbon atoms substituted with halogen, methoxy or phenyl, alkenyl having 2 to 3 carbon atoms, alkynyl having 2 to 3 carbon atoms, aryl or aryl substituted with halogen, nitro or methyl; each of R and R represents hydrogen or methyl; X represents halogen, nitro or methyl; n represents integer of -3; Y represents oxygen or sulfur and M represents metal) are prepared in accordance with the following equations:

3,759,308 Patented Oct. 30, 1973 wherein M represents alkali metal atom and the novel compounds have broad fungicidal activity with very low mammalian toxicity.

This application is a continuation-in-part of United States patent application Ser. No. 771,269, filed Oct. 28, 1968.

This invention relates to novel bisthioureido-benzenes having superior fungicidal activity and to a process for the preparation of the same. Further, the invention relates to fungicidal compositions containing one or more of said novel compounds and further includes methods for combatting fungi with the same compounds.

The novel compounds in the present invention are characterized by one of the following formulas:

(wherein each of and R represents a monovalent radical selected from the group consisting of alkyl of 1 to 12 carbon atoms; alkyl of 1 to 2 carbon atoms substituted with halogen, methoxy or phenyl; alkenyl having 2 to 3 carbon atoms; alkynyl having 2 to 3 carbon atoms; aryl or aryl substituted with halogen, nitro or methyl; each of R and R represents hydrogen or methyl; X represents halogen, nitro or methyl; n represents an integer from 0 to 3; Y represents oxygen or sulfur and M represents a metal atom). The compounds have superior fungicidal activity against various plant diseases such as rice blast disease, cucumber anthracnose, cercospora leaf spot of sugar beets and rice sheath blight disease. It is an advantage of the invention that said compounds have very low mammalian toxicity.

The compounds of this invention can be prepared by the reactions illustrated below, wherein R, R R R X, Y and n are defined as above:v

ZSCN- -C-Y-R NH (8.)

1 x. R s o The reaction Equation 1 is carried out in an inert organic solvent such as acetone, methylethylke't'one, methanol, ethanol, dioxane, acetonitrile, benzene or toluene, at a temperature of 0-150" 0., preferably 10-60 C., ordinarily in about ten minutes to one hour, but occasionally in several hours. After the reaction ends, the compound is isolated from the reaction mixture by conventional techniques. For example, the reaction mixture may be cooled or added to water. The precipitated material is separated from the solution by filtration. Instead, solvent may be distilled off from the reaction mixture. If necessary, the prepared compound may be further purified by washing with water and by recrystallizing from a solvent such as a etone, methanol, ethanol and dioxane.

The reaction Equation 2 is carried out smoothly in aqueous solution at normal room temperature. After the reaction, precipitated material is separated from the solution by conventional procedures, such as filtration. The desired product may be obtained by washing the precipitate with water and hot acetone. The reaction Equation 2 is preferably carried out when the sulfate or the chloride of Cu Ca or Ba is used to supply M++.

In order to facilitate a clear understanding of the invention, the following preferred specific embodiments are described as illustrative and not as limiting the invention.

EXAMPLE 1 1,2-bis-(3-ethoxycarbonyl-2-thioureido)-benzene (Compound 2) containing the resulting ethoxycarbonylisothiocyanate was cooled and kept at a temperature of 20 C. on an ice water bath under agitation. 15.5 g. (0.143 mol.) of ophenylenediamine were dropped into the mixture, while it was maintained at a temperature of l020 C. on an ice water bath under agitation. Then the reaction mixture was kept at room temperature for one hour, and allowed to stand to precipitate a large quantity of crystals. The re action mixture was filtered, and the recovered crystals were washed with water and dried.

47 g. of crystals were obtained. The crystals were light yellow, and had a decomposition point of 190191 C. Colorless plates having the decomposition point of 194 C. were obtained by recrystallization from acetone.

EXAMPLE 2 4-nitro- 1,2-bis- 3-ethoxycarbonyl-2-thioureido benzene (Compound 7) 19.0 g. (0.175 mol. of ethyl chloroformate were added to 18.0 g. (0.185 mol.) of potassium thiocyanate in 150 ml. of acetonitrile at room temperature under agitation, and the mixture was heated and kept at a temperature of 35-45 C. on a water bath. 12.3 g. (0.08 mol.) of 4nitro-o-phenylenediamine were dropped into the mixture containing the resulting ethoxycarbonylisothiocyanate, while it was maintained at a temperature of -30 C. The reaction mixture was heated on a steam bath for one hour under reflux. Then the reaction mixture was cooled and about 500 ml. of cold water was added thereto.

33.0 g. of crystals were obtained following the procedure of Example 1. Light yellow needles having the decomposition point of 205-206 C. were obtained by recrystallization from acetone.

4 EXAMPLE 3 1,2-bis-(3-(Z-methoxy)-ethoxycarbonyl-2-thiouredio)- benzene (Compound 11) 13.8 g. (0.1 mol.) of 2 methoxyethylchloroformate were added to 10.8 g. (0.11 mol.) of potassium thiocyanate in ml. of acetone at room temperature under agitation, and the mixture was heated and kept at a temperature of 40-45 C. for one hour on a water bath. 4.0 g. (0.037 mol.) of o-phenylenediamine were dropped into the mixture containing the 2-(methoxy)-ethoxycarbonylisothiocyanate produced from said reactants while the mixture was maintained at a temperature of 10-20 C. on an ice water bath. The reaction mixture was heated on a steam bath for one hour under reflux. Then the reaction mixture was cooled to room temperature and about 300 ml. of water was added to the cooled mixture.

14.0 g. of the crystals which formed were recrystallized from acetone to obtain colorless needles having M.P. -171" C.

EXAMPLE 4 1,2-bis- 3 -ethylthiocarb onyI-Z-thioureido) -benzene (Compound 13) 8.7 g. (0.07 mol.) of S-ethyl chlorothiol forrri'ate were added to 7.8 g. (0.08 mol.) of potassium thiocyanate in 60 ml. of dioxane at room temperature under agitation, and mixture was heated and kept at a temperature of 35- 40 C. for 30 minutes. 3.3 g. (0.03 mol.) of o-phenylene: diamine were dropped into the mixture while it was kept at a temperature of 1020 C. The resulting reaction mixture was kept at room temperature for one hour under agitation. Then dioxane was distilled oif from the mixture and about 200 ml. of water were added to the residue.

8 g. of the resulting light yellow crystals were recrystallized from dioxane to obtain colorless prisms having decomposition point of 191-192 C.

EXAMPLE 5 1,2-bis-(3-ethoxycarbonyl-2-thioureido)- benzene (Compound 28) 59 g. (0.16 mol.) of 1,2-bis(3-ethoxycarbonyl-2-thioureido)-benzene were added to 13 g. (0.32 mol.) of caustic soda in 700 ml. of water at about 20 C. under agitation. The mixture was agitated for 15 minutes and then filtered. 40 g. (0.16 mol.) of crystallized cupric sulfate EXAMPLE 6 Calcium salt of 1,2-bis-(3-ethoxycarbonyl-2- thioureido)-benzene (Compound 26) I 67.5 g. of powder were obtained according to a procedure similar to that of Example 5, except for 26.5 g. (0.18 mol.) of crystallized calcium chloride in 200 ml. of water instead of 40 g. (0.16 mol.) of crystalli'zed cupric sulfate in 300 ml. of water. The powder was colorless and hada decomposition point of 178- 180 C. (d). 60 g. of a colorless powder having a decomposition point of 169-171 C. were obtained by washing the fi'rst' powder three times with 200 ml. of hot acetone.

Some typical compounds of the present invention are listed in Table 1, along with some of their properties.

Copper salt of Analysis, percent I 1 n-o-Nn-e-o-cmcm),

i-o-cmcmu II II Nn-c-NH-o-o-omomcm The se 4typiea1 compounds Table 1 include merely some of the compounds of the present invention, so that No. of

pound Pale yellow 197-198 (d) cn aNaoa a tablets.

Pale yellow 175-176 (d) CuHaN4O4Sz powder.

Light yellow 206-205.5 (d) CH UNiOG I plates.

206-207((1) ounuohmolsl 180-181 cn -u hNs l a nus-111.5 CxoHuN4Ou Llght brown es.

Pale brown powder.

Colorless prlsms.

Colorless needles.

TABLE I-Contlnued Melting point or .decomposl- Analysis, percent tlon point Molecular Appearance (d) C.) formula H No of compound Structural for mula .do. 180 ao mNsoo s Pale yellow 176477 ((1) 015 20114048:

plates.

177-178 a cummlols.

Colorless plates.

178-180 (d) cumcamms:

Colorless powder.

Light yellow 310 CuHuBaN|04 powder.

Dark green 138-139 ((1) CnHuCuNdhS:

powder.

Analysis, percent 35.29 3.08 14.72 (35. 25) (3.17) (14.68

point Moleeular C.) formula 175 (d) CllHliCiCllNlOdSI TABLE IC0ntlnued Melting point or decompo tion Appearance (d) ....-do...--.. 300 (d) CuHuCuNa a z Light yellow 175 (d) CUHHCBNIOISI powder. ii

Colorless 161-162 a mumps.

powder.

Green 144((1) CuHnCllNaOtS:

powder.

181 (d) CX2HIIBBNAOIS Structural formula NH-C o-ooim OzN No. of compound this invention vary and they are, for example, used in a range of 10-80 weig r, 10-70 weight 150 (d) CuHuCaNaGaSa powder.

and diseases. The concentrations of the active ingredients in the fungicidal compositions of according to type of formulation,

ht percent, preferably 60 weight percent, in wettable powde Light green powder.

/N\ Colorless Nn-c i-ocmcn=cm N -OCH:CH=CH1 The compounds listed in Table I possess very superior fungi ds.

all but effective amount ace by spraying, ol the microbes 75 20- cidal activity compared to known compoun In this invention usually a 5111 of the compounds is applied to plant surf drenching or dusting to protect or contr combating fungi and bacteria. Furthermore, the composi- 1 tion may be applied as a mixture with other fungicides, insecticides, acaricides, plant growth regulators and fertilizers.

The non-limiting examples for the fungicidal compositions are illustrated as follows:

EXAMPLE 7 Wettable powder Parts by weight Compound 2 30 Sodium alkylsulfonate 5 Diatomaceous earth 65 These were mixed and micronized in jet pulverizer to a particle size of 10-20 microns. In practical use, the

micronized mixture is diluted to a concentration of 0.01 to 0.05% of active ingredient with water. The suspension is applied as spray or drench.

EXAMPLE 8 Emulsifiable concentrate Parts by Weight Compound 23 1 Xylene 45 Cyclohexanone 39 Phenyl polyoxyethylene 6 These were mixed and dissolved. In practical use, the solution is diluted with water to a concentration of 0.01 to 0.05% of active ingredient and this suspension is sprayed or used for drenching.

EXAMPLE 9 Dust formulation Parts by weight 2 Compound i Talc 98 These were mixed and crushed to fine powder. The dust formulation is usually applied as dusting powder at a rate of 3 to 5 kg. per 10 are.

In the Examples 7-9, it is not intended to limit the emulsifying, wetting or dispersing agents, carriers and solvents to the ones described by way of illustration.

With regard to mammalian toxicity of the typical compound, for example, that of compound 2 in Table 1 is 15,000 mg./kg. and that of compound 1 is up to 3,000 mg./ kg. as the value of acute order LD 50 for mice.

The superior fungicidal effects of the novel compounds of this invention are clearly illustrated by the following tests.

TEST 1 Test for control of rice blast disease The compound to be tested was applied as waterdiluted solution of wettable powder prepared according to the method of Example 7. The potted rice plants grown to a 3 leaf stage were sprayed at a rate of cc./ pot with solutions of the test materials. One day later, the plants were inoculated with a spore suspension of rice blast fungus, Piricularia oryzae, and held under the condition of incubation (at about 100% relative humidity and 26 C.) in a wet cabinet for 24 hours. Then the plants were moved to a greenhouse bench. Ten days after incubation, number of lesions per pot were examined and evaluation TABLE 2 Cone. of Average active No.o I Control Phytoingredient lesion value tox- (v/ml.) per pot (percent) icity Compound No;

2 500 2.5 97 5 None.- 300 1.0 99 Do. 500 3.5 96.5 Do. 500 0.0 100 Do. 500 12.5 87.4 D0. 500 3.0 97 Do. 500 16.0 83.8 Do.= 500 1.0 99 Do. 500 4.0 96 D0. 500 0.5 99.5 D0. 500 0 100 Do. 500 0 100- R0. 500 0 100 Do. 500 2.2 97.8 Do. 500- 0 100 Do. 500 O 100 D0. 500 0 100 Do. 500 4.0 96.0 Do.

TEST 2.

Test for control of cucumber anthracnose The potted cucumber plants grown to a 3 leaf stage were sprayed at a rate of 50 ml. per 3 plants with waterdiluted solution of the wettable powder prepared by the of percent disease control was based upon the percentage method of Example 7. One day later, the plants were inoculated with a spore suspension of cucumber anthracnose fungus, Colletotriclzum lagenarium, and held under the condition of incubation (at about relative humidity and 26 C.) in a wet cabinet for 20 hours. Then the plants were moved to a greenhouse bench. Seven days after incubation, average number of lesions per leaf were counted and evaluation of percent disease control was based upon the percentage of lesions occuring on the untreated check. The results are shown in Table 3.

TABLE 3 Average Cone. of No. of Control Phyto active ingrelesion per value toxdient ('ylml.) pot (percent) icity Compound N 0.:

1 300 8.2 97.3 None. 300 0.0 100 D0. 300 10.5 96.7 Do. 300 0.0 100 Do. 300 0.0 100 Do. 300 0.0 100 Do.

' TEST 3 Field test for control of Cercospora leaf spot of sugar beets This test was conducted in an attempt to determine the effect of inhibition in development of the Cercospora leaf spot on leaves of sugar beets by the foliage spraying. The field was arranged in a randomized-block design with 4 replicate plots of each treatment consisted of 25 m? per plot. The diluted sprays were applied at the rate of 100 liters per 10 are as a single application after incipient infection was apparent in the leaves. One month after spraying, disease data were taken by counting the infected leaves on 50-60 sugar beets selected at random from each plot and leaf spot severity was rated on a scale ranging from 0 to 5 in which-0 ae.--leaf spot and 5==most of the leaves dead from disease. The results are shown in Table 4.

1 TPTA=Triphenyltin acetate.

15 TEST Test-control of-rice sheath-blight disease The compounds to be tested were applied as waterdiluted solution of wettable powder prepared by the method of Example 7'. The potted rice plants (24-25 plants per single pot) grown to a 5 leaf stage were sprayed at'a rate of 25 cc./ pot with solution vof the test material. Two days later, the plants were inoculated with mycelia of the rice sheath blight fungus, Cortz'cium sasaki, grown-in a culture medium. The plants were transferred to a wet cabinet and held under the condition of incubation (at 100% relative humidity and 25-30 C.) for two days. At the end of this time, the plants were moved to a greenhouse bench. Eight days after incubation, number of plants infected were examined in each test pots and the data were recorded as infection rating made on a scale of =no infected; 1-=up to plants infected/pot; 2=615 plants infected/ pot; 3:16 or more plants infected/pot. The results are shown in Table 5.

' TABLE 5 Cone. of

active ingredient (r/ Phytotoxicity Conipound number:

essssssssssssssssss ZZEZEZQZQQZZZEZEZZZZZ We claim: 1. A compound represented by the formula:

llll

16 wherein each of R and R represents a member selected from the group consisting of alkyl with 1 to 12 carbon atoms, alkyl with 1 or 2 carbon atoms substituted with halogen, methoxy or phenyl, alkenyl with 2 to 3 carbon atoms,'alkynyl with 2 to 3 carbon atoms, aryl, aryl substituted with halogen, nitro or methyl; each of R and R represents hydrogen or methyl; each X represents halogen,

'nitro'or methyl; n represents an integer from O to 3; each Y'represents oxygen of sulfur.

2. A compound according to claim 1 in which n equals zero, each of R and R are hydrogen and each of R and R are alkyl with upto 12 carbon atoms.

3. A compound according to claim 1 in which n equals zero, each of R and R is hydrogen and each of R and R represents alkyl ofl to '2 carbon atoms substituted with halogen, methoxy or phenyl.

4. A compound according to claim 1 in which n equals zero, each of R and R are hydrogen and each of R and R represents aryl substituted with halogen, nitro or methyl. 7

5 A compound according to claim 1 in which each Y is oxygen.

6. A compound according to claim 1 in which n equals zero, each of R and R are hydrogen, each of R and R 5 is CH and Y is oxygen.

7. A compound represented by the formula References Cited Butler 260-438.1

HELEN M. S. SNEED, Primary Examiner 

